The Herbal Medicine Tokishakuyakusan Increases Fetal Blood Glucose Concentrations and Growth Hormone Levels and Improves Intrauterine Growth Retardation Induced by Nω-Nitro-L-arginine Methyl Ester

Abstract

Abstract. N ω -Nitro-L-arginine methyl ester (L-NAME) induces a pre-eclampsia-like syndrome in pregnant rats. We have previously reported the anti-hypertensive effects of several Japanese traditional (Kampo) medicines in this model, and one of these, Tokishakuyakusan (TS), also improved intrauterine growth retardation (IUGR). In the present study, we characterized the effect of TS on IUGR. TS administration reversed the decrease in fetal body weight and fetal blood glucose concentration induced by the infusion of L-NAME. Growth hormone (GH) levels in the fetal blood, which were decreased by L-NAME infusion, were also significantly elevated by TS; however, levels of GH releasing hormone (GHRH) and insulin-like growth factor I (IGF-I) were unchanged and only slightly changed, respectively. Treatment with L-NAME with or without TS had no apparent effect on GH, GHRH, and IGF-I levels of dams. In an immunocytochemical study, the number of GH-positive cells in the fetal pituitary gland was significantly increased in TS-treated rats. These data suggest that enhanced proliferation of somatotrope cells of the pituitary gland and the resultant increase in GH secretion in the fetus may be involved in the improvement of IUGR by TS.

Maternal Hyperglycemia Directly and Rapidly Induces Cardiac Septal Overgrowth in Fetal Rats

“…At this time, blood glucose was lower in the right-sided fetuses (57 ± 8 mg/dL) than in maternal blood (102 ± 4). These right-sided fetal blood glucose levels would be considered hypoglycemic by postnatal standards but are considered euglycemic for late gestational fetal rats which typically have mean blood glucose levels near 50 mg/dL [ 31 – 34 ]. By contrast, left-sided fetuses had 128 ± 58% higher glucoses (131 ± 33 mg/dL) than right-sided fetuses ( Figure 1(b) ).…”

Effects of Sildenafil in Nω-Nitro-l-Arginine Methyl Ester-Induced Intrauterine Growth Restriction in a Rat Model

“…But the increase in blood pressure secondary to L-NAME has been previously established. [42][43][44] Boluses of sildenafil were previously shown to decrease blood pressure and increase the heart rate in both normal and IUGR pregnancies, probably secondary to further vasodilation of the already dilated vascular beds. 24 Another limitation is the small sample size of the offspring in each group, which prohibited the use of more appropriate statistical tests for analyzing the effects in the fetuses considering the dams as the experimental unit.…”

A Combined Supplementation of Omega-3 Fatty Acids and Micronutrients (Folic Acid, Vitamin B12) Reduces Oxidative Stress Markers in a Rat Model of Pregnancy Induced Hypertension

“…The term ‘animal model of preeclampsia’ is commonly and consistently used when nitric oxide synthase inhibitor NG-nitro-L-arginine methylester (L-NAME) was administered from d14 of gestation to induce preeclampsia-like syndrome in rats [40] – [45] . It has been reported that although chronic treatment with L-NAME may not reproduce the entire disease entity, it produces virtually all the pathophysiologies of preeclampsia in the animal model [46] . In view of this the L-NAME induced rat model of pregnancy induced hypertension was used.…”